Biomarkers and use of MET inhibitor for treatment of cancer

Abstract

The present invention relates to methods of therapeutic treatment of cancer using selective tyrosine kinase inhibitors and cancer biomarkers, such as MET amplification and high Met expression for patient selection.

What is claimed is: 
     
       1. A method of treating a patient diagnosed with gastric cancer, wherein a sample of tumor cells obtained from the patient:
 (i) has the presence of focal amplification of the MET gene; and 
 (ii) does not have a mutation at the KRAS gene; 
 wherein the presence of focal amplification of the MET gene is defined by FISH as a ratio of MET gene copy number to chromosome 7 copy number; and 
 wherein the ratio is 2 or higher, 
 the method comprising administering to the patient an amount of 
 (6-{(1R)-1-[8-fluoro-6-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[4,3-a]pyridin-3-yl]ethyl}-3-(2-methoxyethoxy)-1,6-naphthyridin-5(6H)-one) effective to provide a therapeutic benefit. 
 
     
     
       2. The method according to  claim 1 , wherein the KRAS gene mutation is G13D, G13C, G12V, G12S, G12R, G12D, G12C, or G12A. 
     
     
       3. The method according to  claim 1 , wherein focal amplification of the MET gene is determined by detecting increased MET gene copy number. 
     
     
       4. The method according to  claim 3 , wherein the MET gene copy number is determined by FISH. 
     
     
       5. The method according to  claim 1 , wherein the ratio is 3 or higher. 
     
     
       6. The method according to  claim 1 , wherein the ratio is 5 or higher. 
     
     
       7. The method according to  claim 3 , wherein the MET gene copy number is determined by PCR, qPCR, RT-PCR, comparative genomic hybridization, or next generation sequencing. 
     
     
       8. The method according to  claim 1 , wherein the presence of focal amplification of the MET gene is defined by Array Comparative Genomic Hybridization as a ratio of MET gene copy number to chromosome 7 copy number. 
     
     
       9. The method according to  claim 8 , wherein the ratio is 2.5 or higher.